Increased blood pressure variability (BPV) is associated with higher cardiovascular risk. The association between BPV and fluid status in hypertensive patients has not been investigated so far. The aim of the present study was to determine the contribution of fluid balance to BPV and impact on endothelial and cardiac functions among primary hypertensive patients.
This is a prospective interventional study conducted in primary hypertensive patients with one-year follow-up. Volume status measurements by a body composition monitor, ambulatory blood pressure (BP) monitoring, echocardiographic and carotid intima-media thickness (CIMT) measurements were performed at enrollment and at twelfth. Patients in one of the two groups were kept negative hydrated during trial with diuretic treatment. Patients in other group were positively hydrated (hypervolemic) at enrollment, antihypertensive drugs other than diuretics (vasodilator agents) were added or intensified according to the BP monitoring. Average real variability (ARV) index was used for establishing the prognostic significance of BPV.
The study population consisted of 50 patients with a mean age of 54.5±8.8 years. At the end of one-year follow-up, patients in negative hydrated group were found to have significantly lower BP, CIMT, left ventricle mass index (LVMI) and systolic and diastolic ARV. More weight gain and higher systolic BP were major risk factors of high systolic ARV. Patients who have improvement in CIMT and LVMI were considered as target organ damage (TOD) recovery present. In negatively hydrated group, TOD significantly reduced during trial. In patients who have TOD recovery, BPV significantly more reduced like systolic and diastolic BP. Significant risk factors associated with the presence of TOD were 24h systolic BP and daytime and night time diastolic ARV and night time diastolic BP.
Addition of diuretic to established treatment or intensified diuretic treatment and keeping patients in negative hydration status resulted in reduction in BPV at twelfth month of follow-up. More weight gain and higher systolic BP are major risk factors of high systolic ARV, but not hypervolemia. BPV, especially diastolic ARV, was significantly associated with TOD.

The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives.

OBJECTIVE: The Mediterranean diet, rich in polyphenols, has shown to be cardioprotective. However the mechanisms involved remain unknown. We investigated whether supplementation with a pomegranate extract rich in polyphenols renders beneficial effects on coronary function in a clinically relevant experimental model and characterized the underlying mechanisms.
METHODS: Pigs were fed a 10-day normocholesterolemic or hypercholesterolemic diet. Half of the animals were given a supplement of 625 mg/day of a pomegranate extract (Pomanox; 200 mg punicalagins/day). Coronary responses to escalating doses of vasoactive drugs (acetylcholine, calcium ionophore, and sodium nitroprusside) and L-NG-monomethylarginine (endothelial nitric oxide-synthase inhibitor) were measured using flow Doppler. Akt/endothelial nitric oxide-synthase axis activation, monocyte chemoattractant protein-1 expression, oxidative deoxyribonucleic acid damage in the coronary artery, and lipoprotein resistance to oxidation were evaluated.
RESULTS: In dyslipidemic animals, Pomanox supplementation prevented diet-induced impairment of endothelial relaxation, reaching vasodilatory values comparable to normocholesterolemic animals upon stimulation with acetylcholine and/or calcium ionophore. These beneficial effects were associated with vascular Akt/endothelial nitric oxide-synthase activation and lower monocyte chemoattractant protein-1 expression. Pomanox supplementation reduced systemic oxidative stress (higher high-density lipoprotein-antioxidant capacity and higher low-density lipoprotein resistance to oxidation) and coronary deoxyribonucleic acid damage. Normocholesterolemic animals elicited similar drug-related vasodilation regardless of Pomanox supplementation. All animals displayed a similar vasodilatory response to sodium nitroprusside and L-NG-monomethylarginine blunted all vasorelaxation responses except for sodium nitroprusside.
CONCLUSIONS: Pomanox supplementation hinders hyperlipemia-induced coronary endothelial dysfunction by activating the Akt/endothelial nitric oxide-synthase pathway and favorably counteracting vascular inflammation and oxidative damage.